DMD Simcyp

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ammon, S.
Right arrow Articles by Mikus, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ammon, S.
Right arrow Articles by Mikus, G.

Vol. 28, Issue 10, 1149-1152, October 2000

SHORT COMMUNICATION
In Vitro Interaction of Codeine and Diclofenac

Susanne Ammon, Oliver von Richter, Ute Hofmann, Klaus-Peter Thon, Michel Eichelbaum, and Gerd Mikus

Dr. Margarete Fischer-Bosch Institute
of Clinical Pharmacology,
Stuttgart, Germany (S.A., O.v.R., U.H., M.E.)
Robert Bosch Hospital,
Department of Surgery,
Stuttgart, Germany (K.-P.T.)
Internal Medicine VI-Clinical
Pharmacology and Pharmacoepidemiology,
University of Heidelberg,
Germany (G.M.)

There is very limited knowledge about possible pharmacokinetic interactions between opioid analgesics and nonsteroidal antiinflammatory drugs (NSAIDs), which are commonly used in combination for the treatment of chronic pain. The major metabolic pathway of the weak opioid codeine is glucuronidation to codeine-6-glucuronide. Therefore we investigated the influence of the NSAID diclofenac on the formation of codeine-6-glucuronide in vitro, using human liver tissue homogenate. The formation of codeine-6-glucuronide exhibited single enzyme Michaelis-Menten kinetics with an average Vmax of 93.6 ± 35.3 pmol/mg/min. A noncompetitive inhibition of codeine-6-glucuronidation by diclofenac was observed with an average Ki of 7.9 µM. These in vitro findings suggest that a pharmacokinetic interaction occurs in vivo, which has to be confirmed by an interaction study in human subjects. It can be speculated that in case of inhibition of glucuronidation, the amount of codeine available for other pathways especially O-demethylation to morphine is increased, resulting in higher morphine serum levels and therefore higher analgesic efficacy.

Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
S. Takeda, Y. Kitajima, Y. Ishii, Y. Nishimura, P. I. Mackenzie, K. Oguri, and H. Yamada
INHIBITION OF UDP-GLUCURONOSYLTRANSFERASE 2B7-CATALYZED MORPHINE GLUCURONIDATION BY KETOCONAZOLE: DUAL MECHANISMS INVOLVING A NOVEL NONCOMPETITIVE MODE
Drug Metab. Dispos., August 1, 2006; 34(8): 1277 - 1282.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
J. J. Engtrakul, R. S. Foti, T. J. Strelevitz, and M. B. Fisher
ALTERED AZT (3'-AZIDO-3'-DEOXYTHYMIDINE) GLUCURONIDATION KINETICS IN LIVER MICROSOMES AS AN EXPLANATION FOR UNDERPREDICTION OF IN VIVO CLEARANCE: COMPARISON TO HEPATOCYTES AND EFFECT OF INCUBATION ENVIRONMENT
Drug Metab. Dispos., November 1, 2005; 33(11): 1621 - 1627.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
V. Uchaipichat, P. I. Mackenzie, X.-H. Guo, D. Gardner-Stephen, A. Galetin, J. B. Houston, and J. O. Miners
HUMAN UDP-GLUCURONOSYLTRANSFERASES: ISOFORM SELECTIVITY AND KINETICS OF 4-METHYLUMBELLIFERONE AND 1-NAPHTHOL GLUCURONIDATION, EFFECTS OF ORGANIC SOLVENTS, AND INHIBITION BY DICLOFENAC AND PROBENECID
Drug Metab. Dispos., April 1, 2004; 32(4): 413 - 423.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
C. King, W. Tang, J. Ngui, T. Tephly, and M. Braun
Characterization of Rat and Human UDP-Glucuronosyltransferases Responsible for the in Vitro Glucuronidation of Diclofenac
Toxicol. Sci., May 1, 2001; 61(1): 49 - 53.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics.